1. Field of the Invention
The present invention relates to therapeutic peptides that possess inhibitory activity towards elevation of serum triglyceride (triacylglycerol) levels, an unavoidable result that occurs upon ingestion of meals containing high composition of fat. Administration of such peptides before or concomitantly with meals allows for less net absorption of fatty acids into the system, thereby contributing to the prevention of various known cardiovascular diseases as well as obesity-related ailments in general.
2. Description of the Related Art
High serum triglyceride level, independent of the well-known risk factor of serum cholesterol, has been regarded as an additional risk factor for developing cardiovascular diseases, including coronary heart disease (Austin M A, Am. J. epidemiol. 129: 249-59, 1989) and atherosclerosis (Patsch J R et al, Arterioscler. Thromb. 12: 1336-45, 1992). A number of pharmaceutical developments have been made to restrict the elevation of serum triglyceride levels to prevent such cardiovascular ailments.
More significantly, the excessive intake of lipid with respect to energy expenditure leads to obesity, which is currently being regarded as one of the prime health concerns in the Western World. Obesity is a complex medical disorder with implications for diabetes, high cholesterol, cardiovascular conditions, some forms of cancer, and is a major cause of premature mortality. Dietary restriction and behavioral changes are key to prevent obesity, however it is now becoming evident that the success in preventing or treating obesity can be increased with pharmaco-therapy. Several drugs have been developed to combat obesity, however most of these are central-nervous system (CNS)-active, and hence have high abuse potential. Therefore, it would be desirable to have a pharmaceutical agent that would not have these dependency complications.
Recently, a group of low molecular weight peptides which were originally obtained and purified from a non-specific enzymatic proteolysate preparation of bovine reticulocyte protein has been shown to inhibit the elevation of serum triglyceride levels (U.S. Pat. No. 5,958,885). The peptides isolated are low molecular weight, i.e. 3-4 residues in length, and are comprised solely of natural amino acids.
Now, retro-inverso technology, in which oligopeptides are synthesised that are similar to naturally occurring oligo-peptides but with mirror image amino acids put in reverse sequence order (Chorev M, Goodman M, TIBTECH 13:438-45, 1995), is a technology that has had limited take-up in recent years. By utilizing non-natural D-amino acids instead of L-amino acids, it can provide an advantage in bioavailability due to inherent resistance against various natural proteases in vivo but there is no expectation for its use to effectively mimic or better the biological action of naturally occurring peptides.